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Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

Original publication

DOI

10.1038/ng.3874

Type

Journal article

Journal

Nature genetics

Publication Date

07/2017

Volume

49

Pages

1113 - 1119

Addresses

MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Keywords

CARDIoGRAMplusC4D, EPIC-CVD, Muscle, Smooth, Vascular, Arteries, Humans, Genetic Predisposition to Disease, Risk Factors, Cell Adhesion, Chemotaxis, Leukocyte, Histone Code, Energy Metabolism, Genotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Female, Male, Atherosclerosis, Coronary Artery Disease, Genome-Wide Association Study